Hyaluronic acid (HA), type III procollagen III (PC-III), type IV collagen IV (IV-C), and laminin (LN) have certain diagnostic value for hepatobiliary diseases. No published studies have compared the diagnostic accuracy of these 4 indicators for the diagnosis of congenital biliary atresia (CBA) in infants. This study aimed to investigate the diagnostic value of HA, PC-III, IV-C, and LN in infants with CBA.From January 2017 to December 2020, 185 infants with nonphysiological jaundice in the Second Department of General Surgery at the Children’s Hospital of Hebei were enrolled in this study. Forty-six infants with CBA (CBA group) and 139 infants without CBA (noncongenital biliary atresia group) were diagnosed using ultrasonography, magnetic resonance imaging, intraoperative exploration, and intraoperative cholangiography. The levels of HA, PC-III, IV-C, and LN in the 2 groups were statistically analyzed. The diagnostic accuracy was determined using receiver operating characteristic curves and by calculating the area under the curve. Univariate and multivariate logistic regression analyses were performed to identify the independent risk factors.Compared to the noncongenital biliary atresia group, the levels of HA, PC-III, IV-C, and LN were significantly increased in the CBA group (P <.05). The receiver operating characteristic analysis showed the optimal cutoff values for HA, PC-III, IV-C, and LN were 162.7, 42.5, 199.7, and 101.2 ng/mL, and the area under the curves were 0.892, 0.762, 0.804, and 0.768, respectively. The sensitivity values for the diagnosis of CBA were 76.82%, 71.61%, 70.32%, and 72.28%, and the specificity values for the diagnosis of biliary atresia were 70.22%, 70.44%, 66.34%, and 68.71%, respectively. In the multivariate model, HA ≥162.7 ng/mL (odds ratio [OR] = 5.28, 95% confidence interval [CI]: 3.15–8.37), PC-III ≥42.5 ng/mL (OR = 4.61, 95% CI: 2.54–7.16), IV-C ≥199.7 ng/mL (OR = 5.02, 95% CI: 2.98–7.64), and LN ≥101.2 ng/mL (OR = 6.25, 95% CI: 2.41–10.07) remained associated with the occurrence of CBA.HA, PC-III, IV-C, and LN have high accuracy for the diagnosis of CBA in infants, and these factors are potential diagnostic biomarkers for CBA.